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Fig. 3 | Journal of Experimental & Clinical Cancer Research

Fig. 3

From: Novel insights into extrachromosomal DNA: redefining the onco-drivers of tumor progression

Fig. 3

Models of the possible ecDNA genesis mechanism. a. ‘Episome’ model. Bidirectional replication of DNA leads to the existence of two replication forks, and the region between them is named the replication bubble. When an error in replication occurs, the replication forks arrest, and the replication bubble drops and transforms into an episome, which further replicates and recombines to form DMs. b. ‘Translocation-excision-deletion-amplification’ model. Two chromosomes translocate before excision and deletion occur in close proximity to the translocation breakpoints. Then, amplification and circularization of the separate fragments lead to the formation of DMs. c. ‘Chromothripsis’ model. The mis-segregation of a chromosome results in the chromosome shattering and subsequent random repair to form DMs, allowing non-contiguous DNA fragments to fuse in the DMs. d. A multistep evolutionary process in the GLC1 cell line. Recombination and duplication of two single-chromosomal ancestral DMs can occur first, and then the new DMs undergo various types of deletion and recombination with another DM of a single-chromosomal source, resulting in multiple DM subpopulations

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